Design and optimization of wall-climbing robot impeller by genetic algorithm based on computational fluid dynamics and kriging model.

In recent years, wall-climbing robots have begun to replace manual work at heights to reduce economic losses and casualties caused by working at heights. This paper designs a negative pressure adsorption type wall-climbing robot and analyzes the internal fluid movement state of its negative pressure device and the force analysis of the robot when it is adsorbed and balanced. Furthermore, through the experimental prototype, the influence of wall material, robot pose, negative pressure cavity shape and sealing method on the adsorption performance of the wall-climbing robot is explored. The computational fluid dynamics simulation (CFD) simulation method and experimental results are used to verify each other, which proves the correctness of the simulation results. Based on the Kriging surrogate model, the functional relationship between the impeller blade outlet angle, the impeller inlet diameter, the number of blades as the design variables, the negative pressure as the dependent variable was established, and the genetic algorithm (GA) was used to optimize it. Compared with the original design, the optimized design results of impeller parameters have increased the negative pressure value from 3534.75 to 4491.19 Pa, an increase of 27.06%.

Deficiency in AIM2 induces inflammation and adipogenesis in white adipose tissue leading to obesity and insulin resistance.

AIMS/HYPOTHESIS: Absent in melanoma 2 (AIM2) is a cytosolic sensor for double-stranded DNA and a tumour suppressor. Binding of double-stranded DNA to AIM2 forms the AIM2 inflammasome, leading to activation of caspase-1 and production of IL-1ß and IL-18. Although inflammasome-independent effects of AIM2 have been reported, its role in energy metabolism is unknown. We aimed to evaluate the effect of AIM2 in energy metabolism and glucose homeostasis. METHODS: Male and female whole body Aim2 knockout (Aim2-/-) mice were used in the current study. Body weight, food intake, body composition, energy expenditure, fasting blood glucose levels, GTT and body temperature were measured at indicated time points. RNA sequencing was carried out on gonadal white adipose tissue (gWAT) in 14-month-old female mice. mRNA and protein levels in tissues were analysed by quantitative real-time PCR and immunoblot. Immune cell infiltration in gWAT was examined by flow cytometry. Stromal vascular fractions isolated from gWAT were used to investigate adipocyte differentiation. RESULTS: Male and female Aim2-/- mice were obese compared with wild-type controls from 7 weeks of age until 51 weeks of age, with increased adiposity in both subcutaneous and visceral fat depots. While there were no differences in food intake, Aim2-/- mice demonstrated decreased energy expenditure and impaired brown adipose tissue function compared with wild-type controls. Fasting glucose and insulin levels were elevated, and Aim2-/- mice were glucose intolerant on intraperitoneal GTT. RNA sequencing revealed marked upregulation of the IFN-inducible gene Ifi202b, which encodes protein 202 (p202) and elevated inflammatory signalling in gWAT of Aim2-/- mice. Increased infiltration of total and Ly6Clow monocytes was noted at 8 weeks of age in gWAT, before the onset of obesity and insulin resistance. Ifi202b knockdown blocked adipogenesis in stromal vascular fractions and reduced inflammation in bone marrow-derived macrophages, demonstrating a key role of p202 in mediating the increased adipogenesis and inflammation in Aim2-/- mice. CONCLUSIONS/INTERPRETATION: These results demonstrate a fundamental role for AIM2 in energy metabolism, inflammation and insulin resistance. Our studies establish a novel link between the innate immunity proteins, AIM2 and p202, and metabolism.

Effectiveness of pharmaceutical care on treatment outcomes for patients with first-time pulmonary tuberculosis in China.

WHAT IS KNOWN AND OBJECTIVE: In this study, the effectiveness of pharmaceutical care on treatment outcomes for patients with first-time pulmonary tuberculosis in China was assessed. METHODS: In this study, patients were randomized either to the usual care (UC) group (n = 72) where patients received routine medical and nursing care or to the pharmaceutical care (PC) group (n = 59) where patients were simultaneously provided with pharmaceutical care. The primary objectives were to evaluate whether treatment outcomes and patient adherence improved more in the PC group than in the UC group. In addition, in PC group, outcomes included the number of patient-reported pharmaceutical care issues and pharmacists' interventions. RESULTS AND DISCUSSION: As compared to the UC group, treatment success rate was improved in the PC group, but the difference was not statistically significant (71% vs 54%; P = 0.137). However, as compared to the UC group, the number of patients who attended all of the scheduled visits was higher in the PC group; the difference was statistically significant (81% vs 60%, P = 0.018). Furthermore, the number of patients who had positive test results for all of the isoniazid tests was higher in the PC group than in the UC group; the difference was also statistically significant (80% vs 50%, P = 0.002). The consumed medication rate was improved in the PC group, but no significant difference was found between the two groups. The patient-reported pharmaceutical care issues mainly included dermatological, gastrointestinal, hepatic, metabolic, sensory, central nervous system and haematological problems. On the basis of clinical examination, laboratory parameters and drug information database, the pharmacists addressed most of these pharmaceutical care issues. WHAT IS NEW AND CONCLUSION: Pharmaceutical care might improve patient adherence for patients with first-time pulmonary tuberculosis in China, and further, rigorously controlled trials are required.

Meta-analysis of the effects of Bifidobacterium preparations for the prevention and treatment of pediatric antibiotic-associated diarrhea in China.

Bifidobacterium preparations are increasingly used for pediatric antibiotic-associated diarrhea (AAD) in China. The aim of this study was to review existing evidence on the efficacy of Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, and CBM databases. Thirty trials met the inclusion criteria. Of the 30 trials, five Bifidobacterium preparations were included. The preparations were all Bifidobacterium based, in combined with Lactobacillus, Enterococcus, Bacillus, Streptococcus or Clostridium strains. The pooled results of the 30 trials, which included 7225 participants, indicated a statistically significant association of Bifidobacterium preparations administration with reduction in pediatric AAD (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.29-0.39; P<0.01). When the meta-analysis was re-performed according to the trials explicitly aiming to prevent or treat pediatric AAD, respectively, the pooled results were similar (Bifidobacterium preparations use for preventing pediatric AAD (n=21): pooled OR, 0.34, 95% CI, 0.28-0.41, P<0.01; Bifidobacterium preparations use for treating pediatric AAD (n=9): pooled OR, 0.32, 95% CI, 0.23-0.43, P<0.01). Subgroup analyses which based on Bifidobacterium preparations variety, clinical condition, or participant's age also showed statistically significant benefit of adjunct Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. The pooled evidence suggested that Bifidobacterium preparations might be efficacious for the prevention and treatment of pediatric AAD in China.

Outcomes of Chinese herb medicine for the treatment of multidrug-resistant tuberculosis: a systematic review and meta-analysis.

Several studies have suggested that Chinese herb medicine (CHM) in combination with chemotherapy has efficacy in the treatment of multidrug-resistant tuberculosis (MDR-TB). The purpose of this meta-analysis was to assess the efficacy of CHM as a concomitant therapy for MDR-TB. Six databases were searched up to October 2014. Controlled trials comparing CHM combined with chemotherapy (treatment group) with chemotherapy alone (control group) for the treatment of MDR-TB were analyzed. Twenty studies, comprising 1823 patients across China, were included in this review. The meta-analysis showed CHM combined with chemotherapy was associated with a superiority in treatment success (odds ratio [OR], 1.33; 95% confidence interval [CI]: 1.15-1.54; P<0.001), and radiological improvement (OR, 1.32; 95% CI: 1.14-1.52; P<0.001). Patients who received CHM combined with chemotherapy were associated with a similar likely to relapse (OR, 0.88; 95% CI: 0.62-1.25, P=0.478). CHM combination with chemotherapy appeared to be associated with a low incidence of adverse effects for MDT-TB treatment. According to the pooled results and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM combined with chemotherapy for treating MDR-TB. More rigorous controlled trials are required to substantiate or refute these early findings.

Protein tyrosine phosphatase 1B inhibition protects against podocyte injury and proteinuria.

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed nonreceptor protein-tyrosine phosphatase that regulates various cellular functions, including migration. Recent studies suggest that an increased migratory phenotype of podocytes may be responsible for proteinuria and foot process effacement. The current study addresses the role of PTP1B in podocyte injury and proteinuria. PTP1B was markedly up-regulated in the glomerulus, notably in podocytes, in three rodent models of podocyte injury. Podocyte-specific ablation of the PTP1B gene ameliorated proteinuria induced by lipopolysaccharide and Adriamycin (doxorubicin). The use of a specific PTP1B inhibitor also protected against lipopolysaccharide-induced proteinuria. In contrast, podocyte-specific PTP1B transgenic male mice developed spontaneous proteinuria and foot process effacement. In cultured mouse podocytes, PTP1B knockdown and/or pretreatment with the PTP1B inhibitor blunted lipopolysaccharide-induced cell migration, activation of Src-family kinases (SFKs), and phosphorylation of focal adhesion kinase at Y397 (pFAK(Y397)), the latter being crucial for cell migration. Lipopolysaccharide-injected mice showed increased glomerular expression of active SFKs and pFAK(Y397), both of which were inhibited by podocyte-specific PTP1B knockout and the PTP1B inhibitor. Moreover, podocyte-specific PTP1B transgenic mice showed increased glomerular expression of active SFKs and pFAK(Y397). In summary, PTP1B up-regulation in podocytes induces a migratory response by activating SFKs and FAK, leading to foot process effacement and proteinuria. Pharmacological inhibition of PTP1B may have therapeutic potential in the treatment of proteinuric diseases.

Role of guanine nucleotide exchange factor-H1 in complement-mediated RhoA activation in glomerular epithelial cells.

Visceral glomerular epithelial cells (GEC), also known as podocytes, are vital for the structural and functional integrity of the glomerulus. The actin cytoskeleton plays a central role in maintaining GEC morphology. In a rat model of experimental membranous nephropathy (passive Heymann nephritis (PHN)), complement C5b-9-induced proteinuria was associated with the activation of the actin regulator small GTPase, RhoA. The mechanisms of RhoA activation, however, remained unknown. In this study, we explored the role of the epithelial guanine nucleotide exchange factor, GEF-H1, in complement-induced RhoA activation. Using affinity precipitation to monitor GEF activity, we found that GEF-H1 was activated in glomeruli isolated from rats with PHN. Complement C5b-9 also induced parallel activation of GEF-H1 and RhoA in cultured GEC. In GEC in which GEF-H1 was knocked down, both basal and complement-induced RhoA activity was reduced. On the other hand, GEF-H1 knockdown augmented complement-mediated cytolysis, suggesting a role for GEF-H1 and RhoA in protecting GEC from cell death. The MEK1/2 inhibitor, U0126, and mutation of the ERK-dependent phosphorylation site (T678A) prevented complement-induced GEF-H1 activation, indicating a role for the ERK pathway. Further, complement induced GEF-H1 and microtubule accumulation in the perinuclear region. However, both the perinuclear accumulation and the activation of GEF-H1 were independent of microtubules and myosin-mediated contractility, as shown using drugs that interfere with microtubule dynamics and myosin II activity. In summary, we have identified complement-induced ERK-dependent GEF-H1 activation as the upstream mechanism of RhoA stimulation, and this pathway has a protective role against cell death.

Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug-resistant tuberculosis: a retrospective study.

This study compared the efficacy of moxifloxacin and levofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China. A retrospective analysis of 158 patients with MDR-TB receiving either moxifloxacin- or levofloxacin-containing regimens was performed. Clinical data from patients were subjected to univariate analysis, stratification and multiple logistic regression to compare the roles of moxifloxacin and levofloxacin in multidrug regimens. In total, 72 patients received 400mg of moxifloxacin once daily and 86 patients received 509.9 ± 79.4 mg (mean ± standard deviation) of levofloxacin once daily together with similar active agents for similar durations. The times to sputum culture conversion were similar. Adverse reactions occurred at comparable rates. The combined treatment success rate was 60.1%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (67.5% vs. 52.0%; P < 0.05). The success rates for the moxifloxacin group were 65.3% (overall), 77.1% (ofloxacin-susceptible cases) and 54.1% (ofloxacin-resistant cases) in comparison with 55.8%, 60.4% and 50.0%, respectively, for the levofloxacin group. No demographic, clinical, bacteriological or treatment characteristics were independent predictors of favourable outcome. Fourteen patients from the moxifloxacin group and twelve patients from the levofloxacin group had bacteriological relapse after treatment cessation. In conclusion, compared with levofloxacin, moxifloxacin did not show superior efficacy when incorporated into multidrug regimens used for the treatment of MDR-TB.

Chinese herbal medicine in treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis.

AIM OF STUDY: There are multimodal and multidisciplinary approaches to treat diabetic peripheral neuropathy (DPN). However, the intractable adverse effects limited their widespread use. Chinese herbal medicine (CHM) is increasingly used for the treatment of DPN. The aim of this study was to review existing evidence on the effectiveness of CHM for the treatment of DPN. MATERIALS AND METHODS: Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, CBM and Wangfan databases. Controlled trials comparing CHM with other medicine for the treatment of DPN were analyzed. RESULTS: Eighteen trials met the inclusion criteria. All trials used vitamin B12 and/or B1 as control. Clinical therapeutic effect, divided by three grades including marked effective, effective and ineffective according to the improved degree of subjective symptom, tendon reflex, and nerve conduction velocity, was the only end point reported in all trials, and thus evaluated. The results showed CHM treatment was associated with a superiority in marked effective (odds ratio [OR], 2.40; 95% confidence interval [CI]: 0.94 to 2.97; p<0.001), and effective (OR, 1.39; 95% CI: 1.16 to 1.67; p<0.001). Patients who received CHM treatment was associated with a less likely to report ineffective (OR, 0.26; 95% CI: 0.21 to 0.33, p<0.001). No adverse events were reported in any of the included trials. CONCLUSIONS: According to the pooled results of our study and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM for treating DPN. More rigorous controlled trials are required to substantiate or refute these early findings.

Podocyte Protein, Nephrin, Is a Substrate of Protein Tyrosine Phosphatase 1B.

Glomerular podocytes are critical for the barrier function of the glomerulus in the kidney and their dysfunction causes protein leakage into the urine (proteinuria). Nephrin is a key podocyte protein, which regulates the actin cytoskeleton via tyrosine phosphorylation of its cytoplasmic domain. Here we report that two protein tyrosine phosphatases, PTP1B and PTP-PEST negatively regulate nephrin tyrosine phosphorylation. PTP1B directly binds to and dephosphorylates nephrin, while the action of PTP-PEST is indirect. The two phosphatases are also upregulated in the glomerulus in the rat model of puromycin aminonucleoside nephrosis. Both overexpression and inhibition of PTP1B deranged the actin cytoskeleton in cultured mouse podocytes. Thus, protein tyrosine phosphatases may affect podocyte function via regulating nephrin tyrosine phosphorylation.

Activation of RhoA in podocytes induces focal segmental glomerulosclerosis.

Proper organization of the actin cytoskeleton is essential for the normal structure and function of podocytes. RhoA modulates actin dynamics but its role in podocyte biology is controversial. Here, we generated transgenic mice that express a constitutively active form of RhoA in a podocyte-specific and doxycycline-inducible manner. Induction of activated RhoA with doxycycline resulted in significant albuminuria. Furthermore, both the degree of albuminuria and the histologic changes in the glomerulus positively correlated with the level of constitutively active RhoA expression: low levels of expression associated with segmental foot-process effacement without changes observable by light microscopy, whereas higher levels of expression associated with both extensive foot-process effacement and histologic features of focal segmental glomerulosclerosis (FSGS). In addition, induction of activated RhoA markedly upregulated glomerular mRNA expression of fibronectin and collagen IA1, and the degree of upregulation positively correlated with the level of albuminuria. Withdrawal of doxycycline led to a decline in albuminuria toward basal levels in most mice, but heavy albuminuria persisted in some mice. Taken together, these data suggest that activation of RhoA in podocytes leads to albuminuria accompanied by a range of histologic changes characteristic of minimal change disease and FSGS in humans. Although most changes are reversible, severe and prolonged activation of RhoA may cause irreversible glomerulosclerosis.

Pulmonary resection for patients with multidrug-resistant tuberculosis: systematic review and meta-analysis.

OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) has become an emerging global public health crisis. Several studies have suggested that pulmonary resection has efficacy in the treatment of MDR-TB. A systematic review of the available therapeutic studies was conducted to determine the treatment outcome among patients with MDR-TB who underwent pulmonary resection. METHODS: To evaluate pulmonary resection for MDR-TB, a random-effect meta-analysis of the available studies was used to assess the overall treatment outcome. Subgroup analyses were also conducted by separating studies based on each characteristic independently. RESULTS: After screening 4996 articles, 15 clinical reports with a mean of 63 patients per report met the inclusion criteria. Analysis of the studies showed that the estimated pooled treatment success rate of pulmonary resection for patients with MDR-TB was 84% [95% confidence interval (CI) 78%-89%]. The rates of failure, relapse, death and default were 6% (95% CI 4%-8%), 3% (95% CI 1%-4%), 5% (95% CI 2%-8%) and 3% (95% CI 1%-5%), respectively. The proportion of patients treated successfully did not differ significantly on the basis of any of the individual study characteristics. CONCLUSIONS: Substantial heterogeneity in the study characteristics prevented a more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. Some important variables, including patient HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR-TB treatment programmes.

[The effect of the regimen containing cefoxitin on highly drug-resistant rapidly growing nontuberculous mycobacterial pulmonary disease].

OBJECTIVE: To evaluate the therapeutic effect and safety of the regimen containing cefoxitin on highly drug-resistant rapidly growing nontuberculous mycobacterial (RGM) pulmonary disease. METHODS: From January to December 2007, 16 patients with RGM pulmonary disease, who had been treated for 6-48 months, average (15 ± 11) months but still sputum positive, were included in the study and treated with a new regimen containing cefoxitin, fluoroquinolone, macrolide, and SMZco. Cefoxitin was used in the first 3 months and the total duration of therapy was 18 months. Sputum conversion rate, radiology change and side effects were observed before and after the therapy. RESULTS: Underlying chronic diseases including COPD (n = 2), tuberculosis (n = 3), bone-marrow transplantation due to chronic leukemia (n = 1) and bronchiectasis (n = 5), were present in 11 patients. Main symptoms before therapy were cough and expectoration. There were multi-focal patchy, small nodular shadows with cavities on CT scans. The 16 clinical strains were highly resistant to anti-tuberculous drugs: 15/16 to streptomycin, 16/16 to isoniazid, 14/16 to rifampin, 13/16 to ethambutol, 14/15 to amikacin, 15/15 to capreomycin and 14/15 to ofloxacin. After treatment, the clinical symptoms improved in all patients. Eight of the 16 patients became sputum negative by 6 months which lasted to the end of the therapy, while another 8 patients remained sputum positive. Six patients showed radiological improvement. No one experienced side effects induced by cefoxitin. The total cure rate was 8/16. CONCLUSION: The regimen containing cefoxitin has certain effect on highly drug-resistant nontuberculous mycobacterial pulmonary disease, especially for RGM.

p21-activated kinases regulate actin remodeling in glomerular podocytes.

The tyrosine phosphorylation of nephrin is reported to regulate podocyte morphology via the Nck adaptor proteins. The Pak family of kinases are regulators of the actin cytoskeleton and are recruited to the plasma membrane via Nck. Here, we investigated the role of Pak in podocyte morphology. Pak1/2 were expressed in cultured podocytes. In mouse podocytes, Pak2 was predominantly phosphorylated, concentrated at the tips of the cellular processes, and its expression and/or phosphorylation were further increased when differentiated. Overexpression of rat nephrin in podocytes increased Pak1/2 phosphorylation, which was abolished when the Nck binding sites were mutated. Furthermore, dominant-negative Nck constructs blocked the Pak1 phosphorylation induced by antibody-mediated cross linking of nephrin. Transient transfection of constitutively kinase-active Pak1 into differentiated mouse podocytes decreased stress fibers, increased cortical F-actin, and extended the cellular processes, whereas kinase-dead mutant, kinase inhibitory construct, and Pak2 knockdown by shRNA had the opposite effect. In a rat model of puromycin aminonucleoside nephrosis, Pak1/2 phosphorylation was decreased in glomeruli, concomitantly with a decrease of nephrin tyrosine phosphorylation. These results suggest that Pak contributes to remodeling of the actin cytoskeleton in podocytes. Disturbed nephrin-Nck-Pak interaction may contribute to abnormal morphology of podocytes and proteinuria.

Rac1 contributes to actin organization in glomerular podocytes.

BACKGROUND/AIMS: The function of glomerular podocytes is closely associated with the actin cytoskeleton. In this study, we studied the role of the small Rho-GTPase, Rac1, in actin organization in podocytes. METHODS: Conditionally immortalized mouse podocytes (MP) stably expressing nephrin or control plasmid were used. RESULTS: In MP, Rac1 activity increased significantly at 1 week of differentiation. MP stably expressing nephrin showed Rac1 activity significantly higher and more sustained than vector-expressing control cells. Antibody-mediated cross-linking of nephrin also activated Rac1. Differentiated MP showed more distinct lamellipodia/cellular processes, as compared with undifferentiated cells, which was further augmented by nephrin expression. Transient transfection of constitutively active Rac1 markedly increased the number of lamellipodia/cellular processes in undifferentiated MP, while the Rac1 inhibitor caused actin cytoskeleton derangement in differentiating MP. In the rat model of puromycin aminonucleoside nephrosis, RhoA activity was increased at Day 7 (at the peak of proteinuria), while Rac1 activity increased significantly only at Day 14, when the recovery process had started. CONCLUSION: Rac1 is activated in differentiating MP and nephrin potentiates Rac1 activation. Rac1 likely contributes to lamellipodia formation in differentiating MP and may contribute to process formation in podocytes recovering from injuries.

Cloning, characterization and prokaryotic expression of cytosolic malate dehydrogenase from Oryza sativa.

cDNA sequences of malate dehydrogenase (MDH) were cloned from various species, and MDH was identified to play an important role in cell energy metabolism. Here, we present the isolation and characterization of its homologue (OscMDH) in Oryza sativa. Comparison of the results to the genome details indicated that OscMDH consisted of seven exons. Sequence alignment showed that the deduced amino acid sequence of OscMDH shared a significant similarity with cMDH protein in Zea mays, as well as with other cMDH gene products. The different expression patterns of OscMDH in different tissues revealed that OscMDH mRNA was highly transcribed in either young panicle or immature seed, while its abundance was much low in green leaf and root. A nearly 56-kDa fusion protein generated by adding a Trx-His-tag at the N-terminal of OscMDH was induced by IPTG in Escherichia coli BL21 and an obvious MDH activity was detected in the protein by native PAGE analysis. All these results suggest that OscMDH encodes a cytosolic MDH in rice.